Adverse Effects of Artificial Sweeteners

Consumption of non-caloric artificial sweeteners can alter the gut microbiota to increase risk for glucose intolerance, according to a study in mice and humans.



A study published online Sept. 17 in Nature showed that non-caloric artificial sweeteners (NAS), among the most widely used food additives worldwide, promote development of glucose intolerance by altering the intestinal microbiota.

Jotham Suez et al fed mice with water that contained either sugar or 1 of 3 NAS (aspartame, sucralose, or saccharin). After 11 weeks, the mice given the NAS developed glucose intolerance. However, those also given antibiotics for 4 weeks did not develop glucose intolerance, indicating a role for gut microbes.

According to a news story in Science, certain types of microbes were more common in intestines of mice fed saccharin. In particular, Suez et al. detected an increase in carbohydrate degradation pathways in the microbiota of NAS-fed mice.

When the researchers took gut bacteria from healthy mice, cultured them with saccharin, and then transferred them into germ-free mice, the recipients also developed glucose intolerance.

Suez et al. propose that molecules produced by some of the bacteria increase glucose production in the body and push blood glucose levels out of balance.

NAS are regularly consumed by lean and obese individuals. Their consumption has been considered safe, due to their low caloric content, yet few data are available to support their safety or efficacy in weight loss.

The Los Angeles Times Science Now blog explained that artificial sweeteners are not digested by the human body, which is why they have no calories. However, they still must pass through our gastrointestinal tract, where they interact with the bacterial ecosystem.

Suez et al. studied almost 400 people and found that the intestinal bacterial populations of those who consumed NAS differed significantly from those who did not. Moreover, NAS consumption correlated with markers of obesity, such as increased fasting levels of blood glucose and impaired glucose tolerance.

The researchers performed experiments with 7 healthy, non-obese volunteers who did not regularly consume artificial sweeteners. For 6 consecutive days, they were given 5 mg/kg of body weight, the Food and Drug Administration’s maximum acceptable daily intake (the Los Angeles Times reported that this was the equivalent of 40 cans of diet soda/day). The volunteers wore a monitor that checked their blood sugar levels every 5 minutes.

After only 4 days, 4 of the volunteers had increased blood levels of glucose and alterations to their intestinal microbiota. Transfer of fecal samples from NAS-fed human donors increased blood glucose levels in germ-free mice that had never consumed NAS.

However, no changes occurred in the other 3 volunteers. A computer algorithm used to analyze the microbes of the 7 people and clustered them into 2 groups: those affected by the artificial sweeteners and those not affected.

In a News and Views article that accompanied the report, Taylor Feehley and Cathryn R. Nagler explain that certain gut bacteria are well adapted to break down dietary components that the human body cannot. It could be that expansion of these populations in response to NAS increases extraction of energy — often stored as fat — from the diet, contributing to obesity. Alternatively, NAS might exert their effect by suppressing the growth of particular bacterial taxa.

Feehley and Nagler say that in obese mice, the growth of certain bacterial species is suppressed, and there is an increased production of metabolites that can contribute to insulin resistance. They propose further studies to determine whether the changes in the microbiota produced by NAS consumption resemble those of obese individuals.

The Washington Post wrote that the findings add an intriguing new dimension to the long-running debate over the potential health benefits and risks of artificial sweeteners, which are consumed by hundreds of millions of people.

Although some studies have found that the products pose no health risks and help people cut calories and sugar intake, others found that certain artificial sweeteners actually contribute to obesity and other problems, including cancer.

Suez et al. propose that artificial sweeteners “may have directly contributed to enhancing the exact [diabetes] epidemic that they themselves were intended to fight.”

According to the Washington Post, the American Medical Association and the American Diabetes Association have cautiously backed the use of non-caloric sugar substitutes as a way to fight obesity and diabetes, saying that they can be part of a healthy diet as long as the calories saved aren’t replaced by more food.

USA Today wrote that “reaching for artificial sweeteners to avoid sugar may be trading one evil for another.”

1 Comment

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    Madelin Siedler September 25, 2014

    I was disappointed to see that the authors did not conduct any further research on the specific effects of aspartame and sucralose, which are by far the most widely used artificial sweeteners today. Interestingly, in the few experiments which studied the effects of aspartame, it seemed to be the most benign of the three. There are only a few graphs shown to illustrate the glycemic response in mice fed these sweeteners, but these graphs don’t seem to include an accompanying table to lay out important data, such as mean AUC among these different groups along with their respective confidence intervals and p values.

    Overall, the authors seem to sweepingly announce their results as being reflective of all sweeteners, which is very misleading, given that the majority of the study’s experiments focused on saccharin only, and given that all three sweeteners are vastly different in their molecular construction. Lastly, even in the supplemental tables, no details are given in regards to the human study that used food questionnaires: exactly what NAS which the human subjects consuming, and at what doses? These things are too important to simply exclude, which makes me wary of the study’s conclusions as a whole. The evidence against saccharin is well presented, but that’s where the discussion of sweeteners as a whole begins and ends.